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http://www.mg.co.za/articlePage.aspx?ar ... _national/

James Randerson

11 March 2007 11:59

Scientists have developed a test for the early diagnosis of lung cancer. They hope that analysis of the genes that are switched on and off in cells lining the airways leading to the lungs can be used to diagnose patients sooner and make treatments more effective.

Lung cancer is the most deadly form of the disease. In Britain, it is the most common cancer in men and the third most common in women. About 37 700 new cases were recorded in 2002 and nearly 29 000 deaths.

Part of the reason it is so lethal is that the disease is often diagnosed late. Patients frequently die shortly after learning they have contracted the disease.

Only one-fifth of patients are alive one year after diagnosis of the disease, which kills 92% of sufferers within five years. The vast majority of people with lung cancer are smokers.

Avrum Spira and his team at Boston University in Massachusetts examined lung tissue collected from 129 current or former smokers.

All were undergoing normal lung examination tests for detecting suspected lung cancer. The tests involved scraping cells from the inner lining of their airways and examining them under a microscope to look for abnormalities.

The team examined the expression of 80 genes in the cells. And, by waiting until the patients were either given the definitive “all clear” or a lung cancer diagnosis, they identified a pattern of gene expression or “biomarker” that was consistently associated with a cancer diagnosis.

The team validated their method with a further 35 samples from patients at five hospitals. “Our biomarker had [about] 90% sensitivity for stage one cancer across all subjects,” they wrote in the current issue of Nature Medicine.

Traditional techniques that look for abnormal features of cells have a sensitivity of around 30% in early stage cancer. Combined with the biomarker, the sensitivity of these techniques increased to 90% as well.

If the technique proves successful in further tests, it could be streamlined into a “DNA chip” that gives a rapid readout of which genes are active in cells taken from the patient.

This could lead to much earlier diagnosis of lung cancers, which would allow doctors to start treatment earlier and give patients a better chance of

surviving the disease. It would also provide an earlier incentive for smokers to give up. “Our biomarker might be useful as a screening tool for lung cancer among healthy smokers,” the authors wrote.

Smoking has numerous other health effects, including greatly increasing the risk of heart disease and triggering lung conditions such as emphysema and chronic bronchitis. -- © Guardian News & Media 2007

Many new cancer genes found

Scientists have found more than 100 new genes that can cause cancer if they become mutated, writes Alok Jha. The discovery was part of the largest survey of the human genome to date, which also suggests that the number of cancer genes is far larger than previously thought.

“Thus far, there are approximately 350 genes in the human genome that have been shown to be cancer genes,” said Mike Stratton, co-leader of the Cancer Genome Project at the Wellcome Trust Sanger Institute at Cambridge in south-east England. “This is from a full spec of around 25 000 genes in the human genome.”

In the new study, researchers looked at more than 500 genes in about 200 samples of different types of cancer. The results, published in the current Nature, showed about 1 000 mutations in the protein kinase (the key controllers of cell behaviour) genes of cancer cells. Based on previous research, Stratton said they had only expected to find about 10 new cancer genes in their sample.

The 1 000 mutations were classified in two categories: drivers and passengers. Driver mutations are the ones that cause cancer cells to grow, whereas passengers make no contribution to cancers.

“It turns out that most mutations in cancers are passengers. However, buried among them are much larger numbers of driver mutations than anticipated,” said Stratton. -- © Guardian News & Media 2007

This suggests that many more genes contribute to cancer development than was thought,” said Dr Futreal. The challenge in the future will be differentiating between driver and passenger mutations.

Another surprise was the way in which the mutations were spread among the cancers - in some samples, scientists found large numbers of mutations in a pattern they had never seen before. “The number and patterns of these mutations are an archaeological signature of something that has happened to that cancer in the past, something that has been implicated in its causation,” said Prof Stratton.

Some of these causes, such as the drug a cancer has been treated with, ultraviolet light and cigarette smoke, can already be interpreted. But Prof Stratton said the new mutations would need further research to explain. “This must be telling us something about previous exposures, perhaps to environmental chemicals and also abnormalities of DNA repair in these cancers.” -- © Guardian News & Media Ltd 2007

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